Recent studies have demonstrated that elevation of serum homocysteine (HC) levels is a risk factor for stroke, coronary artery disease, and peripheral vascular disease. HC levels are largely controlled by the levels of three water-soluble vitamins; folate, B12, and B6 (pyridoxal-5'-phosphate, PLP). We have recently demonstrated that PLP levels are low in patients with rheumatoid arthritis (RA) compared to age-matched controls, and that PLP levels correlate with production of tumor necrosis factor (TNF) by mononuclear cells from these patients (1). In a second recently completed study, we found that patients with RA and low circulating PLP levels had elevated fasting levels of HC and an abnormally high increase in HC after challenge with an oral dose of methionine. These results indicate that patients with RA may have tissue deficiency of PLP and be at risk for the vascular complications of elevated HC.